I-PRN1008

Igama Lekhemikhali:

(S)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4 -methyl-4-(4-(oxetan-3-yl)piperazin-1-yl)pent-2-enenitrile

Ikhodi ye-SMILES:

NC1=C2C(N([C@H]3CCCN(C(/C(C#N)=CC(C)(N4CCN(C5COC5)CC4)C)=O)C3)N=C2C6=C(F)C =C(OC7=CC=CC=C7)C=C6)=NC=N1

Ikhodi ye-InChi:

I-InChI=1S/C36H40FN9O3/c1-36(2,45-15-13-43(14-16-45)26-21-48-22-26) 18-24(19-38)35(47)44-12-6-7-25(20-44)46-34-31(33(39)40-23-41-34)32 (42-46)29-11-10-28(17-30(29)37)49-27-8-4-3-5-9-27/h3-5,8-11,17-18, 23,25-26H,6-7,12-16,20-22H2,1-2H3,(H2,39,40,41)/b24-18-/t25-/m0/s1

I-InChi Key:

I-LCFFREMLXLZNHE-IEUUHXEXSA-N

Igama elingukhiye:

I-PRN1008, PRN-1008, PRN 1008,1575596-29-0

Ukunyibilika:I-Soluble ku-DMSO

Isitoreji:0 - 4°C isikhathi esifushane (izinsuku ukuya emavikini), noma -20°C isikhathi eside (izinyanga).

Incazelo:

I-PRN1008 iyi-covalent inhibitor enamandla, ekhethayo futhi ehlehlayo ye-BTK ((IC50 = 1.3 ± 0.5 nM).) enemiphumela enwetshiwe ye-PD ku-vivo. I-PRN1008 yayiphephile futhi ibekezelelwa kahle ngemva komthamo owodwa kanye nezinsuku eziyi-10 kubantu. Ukudosa ukuze uthole ukuhlala okungu-> 90% ngemva komthamo kubangela ukuhlala okuhlosiwe okungaguquki nesikhathi eside. Ukufakwa okuhlosiwe kwe-BTK okunomthamo wansuku zonke ongu-≥300mg kufinyelele kumazinga okwelapha asekelwe ezifundweni zokuhumusha kumodeli yegundane yesifo samathambo. Lezi datha zisekela ukuthuthukiswa okuqhubekayo kwe-PRN1008 njenge-ejenti yokwelapha ye-rheumatoid arthritis.

Ithagethi: BTK